The mechanism of action of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is being studied in several animal species. In primates, MPTP produces a persistent parkinsonian syndrome. Neurochemical studies have demonstrated a close correspondence between idiopathic Parkinson's disease in humans and MPTP toxicity. Metabolism of 14C and 3H MPTP has been studied in four monkeys, sacrificed at times varying from 24 hrs to 20 days. MPTP appears to be metabolized in monkey brain by oxidation to 1-methyl-4-phenylpyridine (MPP) which is trapped intraneuronally. MPP+ persists in brain with a half-life of 10 days at micromolar concentrations and may be responsible for MPTP neurotoxicity. In contrast, in the guinea pig and rat, MPTP is rapidly metabolized without accummulation of MPP in brain. The in vitro oxidation of MPTP to MPP has been characterized. The acute and chronic actions of MPTP in the rat have been characterized. MPTP exhibits acute tryptamine-like effects in the rat, but regardless of the mode of administration, fails to produce a permanent neurotoxicity as observed in the monkey. The opiate properties of MPTP and the intended synthetic heroin substitute, 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP) have been characterized. It has been shown that MPPP is a potent analgesic which probably masked the slowly developing neurotoxicity of MPTP in drug abusers. MPP is being studied to determine whether it or its generation is required for expression of neurotoxicity.